The long-term goals of the Principal Investigator and the Foreign Collaborator are to understand the molecular basis of sperm fertilization competence. The PI has focused in his research on the signal transduction mechanisms underlying sperm capacitation, which requires a maturation process that occurs during their transit through the epididymis. The foreign investigator has studied the biochemistry and cell biology of epididymal maturation. Together, these investigators have demonstrated an apparent maturation of the signal transduction mechanisms in parallel with epididymal maturation. The aims of this proposal are to 1) determine whether sperm epididymal transit is associated with alteration of cholesterol efflux in response to serum albumin and beta cyclodextrins, agents that bind cholesterol in vitro, 2) determine the mechanisms by which epididymal maturation regulates the response of the sperm to db-cAMP leading to protein tyrosine phosphorylation, and 3) determine whether the oxidation state of the epididymal environment can influence the maturation of the signal transduction machinery that regulates sperm capacitation. The results of these experiments may aid in the understanding of epididymal maturation and its role in fertilization competence, which may relevant to both male infertility and contraception.